The invention relates to a packaging device and electronic use-monitoring system for items intended to be dispensed over a period of time or on a particular schedule, such as prescription medications.
Medications, including prescription and over-the-counter pharmaceuticals, as well as vitamins and other dietary supplements, form a mainstay of health care, maintenance, and disease management and prevention. Typically a medication is given in repeated oral doses, usually as pills (here taken to include capsules), spread out over time so as to sustain desired levels of active ingredients in the patient's body. Any substantial deviation from the recommended timing, such as missing a dose or “doubling up” on doses, may decrease a medication's effectiveness or cause outright harm to the patient.
Pills have historically been provided to patients in bottles, each bottle containing only one type of pill, with the dosing recommendations written or printed on the label but with no means to ensure the patient has, in fact, followed those recommendations. For a healthy, alert and non-addicted patient taking one or just a few types of medication, that protocol is usually satisfactory. With patients, however, who are elderly, distracted by pain, or mentally dulled—sometimes by the very drugs they are taking—and especially for those who are simultaneously on several different medications, the frequency of errors can increase dramatically. A patient directed to take two pills from a first bottle and one from a second, for example, might mistakenly take one from the first and two from the second instead. Patients are unlikely to report such errors to their physicians.
As lifespans increase and the average patient age rises, and as individual patients are prescribed increasing numbers of different medications, errors can be expected to pose an ever-worsening problem.
To minimize these errors, a growing trend for pharmacies is to package medications not “by kind” in prescription bottles, but “by dose”: placing medications to be taken at the same time together, but separated from those to be taken at other times. Typically, each pill or group of pills is held in a molded plastic blister attached to a card, with separate blisters holding doses to be taken at different times. For example, a patient might receive a card with twenty-eight separate plastic blisters, half ringed in red and half in blue, representing a two-week supply of several prescriptions combined. Red-ringed blisters would then be opened and the medications in them taken in the morning, blue-ringed ones in the evening before retiring.
Blister packaging for prescription drugs has been common in Europe for a decade or more, and is slowly penetrating the U.S. market as well. Many pharmacies will provide blister packaging of prescriptions “by dose” on request, for a small extra fee. Blister packaging is also widely used for over-the-counter (OTC) medications, especially where exceeding recommended doses could be hazardous.
Advantages of blister packaging include better protection of product integrity and quality, better tamper evidencing and child resistance, and improved patient compliance since “by dose” packaging helps eliminate confusion.
A further complication results from the fact that many medications now prescribed for patients are also targets for abuse, and of those, many are addictive. Pain medications such as opiates and oxycodone are obvious examples. A patient dissatisfied with the relief from a single pill might decide to take two or more at once and, after a time, find even that dose ineffective. Such use of ever-greater doses could lead to addiction. Conversely, on no longer needing the pills the patient might decide to sell them instead, or pass them along to a friend. Or, medications might be diverted by a third party for sale.
To ensure that medications are being taken on the prescribed schedule—and thus, presumably, also by the intended patient—a blister pack can be fitted with electronic means for detecting the opening of each blister and recording the time at which it was opened. Other high-value, potentially hazardous or diversion-prone items could be packaged and monitored similarly. Blasting caps, for example, might be blister-packed and electronically monitored to create a record of when each had been removed from the package. Monitoring in this case would create a record of removal for use and prevent, or at least detect, any unauthorized use or diversion.
While many detection schemes have been proposed, the only ones which appear cost-effective, and those most often seen in the prior art, have relied on the breakage of conductive traces in a printed-circuit-like array formed on a card or other substrate which supports the blisters, and through which an opening must be made to access the contents of each. These schemes in turn fall into two main groups: digital approaches where each trace uniquely identifies one of the blisters and by its breakage signals that that blister has been opened, and analog ones where a resistance is altered in stages as successive blisters are opened.
FIG. 1 illustrates a typical prior-art digital electronically monitored card, while FIG. 2 shows the corresponding circuit as a schematic diagram. While in an actual embodiment the blisters might number several dozen, for clarity in these Figures only three blisters and their associated circuitry are shown.
A sheet 10, typically made of stiff clear plastic, is impressed with blisters 12a, 12b, 12c and so forth. Closing the backs of these blisters is a sheet 14 of paper, foil, plastic, light cardboard or other air- and moisture-tight but easily broken material having a nonconductive surface 16 serving as the substrate on which a plurality of electrically conductive traces 20a, 20b and so forth, much like those on a printed circuit board and all having roughly equal conductivity, are formed by any of several methods well-known in the art of creating conductive circuit paths, including but not limited to screen, pad, flexographic and ink-jet printing with conductive inks, mechanical engraving, die-cutting or etching of foil, and chemical or vapor deposition. While surface 16 bearing these traces is shown in FIG. 1 as located on the side of sheet 14 opposite blisters 12a, 12b, 12c and so forth, it could equally well be located on the side of sheet 14 facing the blisters, or nonconductive trace-bearing surfaces could be located on both sides of the sheet.
Traces 20a, 20b and so forth connect with an electronics module 30 containing a monitoring system usually including batteries, a simple microcontroller, nonvolatile memory such as EEPROM or flash memory, and means such as a USB port for connection to an external computer. One, and only one, trace crosses the sheet behind each blister and typically there forms a zig-zag, labyrinthine or otherwise spatially extended pattern 32a, 32b, 32c and so forth, covering substantially the entire back of the corresponding blister 12a, 12b, 12c or the like and thus ensuring that the trace will be broken no matter how sheet 14 is cut or torn to open the blister. For purposes of illustration, traces 32a and 32b are shown as intact in FIG. 2 while trace 32c is shown as broken.
At least one other trace, exemplified in FIGS. 1 and 2 by trace 20a, does not form such an extended pattern and is not expected to be broken when blisters are opened. Instead, this trace forms a common bus 34 connected to a plurality of the pattern-forming traces. The dashed line extending to the right from bus 34 in FIG. 2 indicates that additional pattern-forming traces beyond the three shown in the Figure will typically be present. Module 30 holds trace 20a and bus 34, at least intermittently, at a first voltage which represents a first logic value to the electronics within the module.
The end 36a, 36b, 36c or the like of each pattern-forming trace opposite to bus 34 is connected to a separate input such as 42a, 42b or 42c of electronics module 30. Each input is so constructed that in the absence of any input, it is weakly pulled toward a second voltage representing the opposite logic state. As a result, when a pattern-forming trace is intact, its connected input reads the logic state corresponding to bus 34's voltage, while if the trace is broken the input receives no external signal and reads the opposite logic state instead.
For example, classical TTL and later logic families designed to be compatible with it read any input voltage above +2.0 volts as logic “1.” Voltages between ground and +0.8 volts are read as logic “0,” while those between +0.8 and +2.0 volts are indeterminate and are normally avoided. To avoid indeterminate voltages on disconnected inputs, TTL-type gates are designed with internal “pull-up” so an input receiving no signal will also be read as logic “1.”
Monitoring system 30 periodically samples the inputs, and counts the number of inputs whose voltages correspond to broken traces. The resulting count, at least in theory, equals the number of blisters opened. If its number differs from the last recorded value, the system records the new number in nonvolatile memory along with the time at which it first appeared. To conserve power, system 30 may then enter a low-power “sleep” mode for some preselected interval of time. At the end of this period, the cycle is repeated. Sampling, and recording data as needed, continues until all blisters have been opened.
The result is a record in memory of all of the times when blisters were opened, along with the number of blisters opened each time. Since the memory is nonvolatile, this record will persist until it is read back out by a suitably programmed computer connected to system 30. The resulting data can be compared easily with the prescribed dosing cycle, for example of a prescribed medication, and patient compliance thus determined.
A disadvantage of this approach is the need for a large number of separate inputs to electronics module 30, one input for each individual blister to be monitored. A greater number of input lines requires either a larger microcontroller, or means separate from the microcontroller for multiplexing many digital signals onto a smaller number of lines. Either of these approaches is likely to increase the system cost.
Another disadvantage is the requirement for a least as many traces as there are blisters, since given any particular trace-forming technology some minimum amount of conductive material will be needed to form each of them and such material is inherently costly. In screen printing, for example, traces are typically formed by the deposition of an ink heavily loaded with powdered silver.
Yet another disadvantage is that the typically close placement of blisters on a card leaves little, if any, space on surface 16 remaining safe from damage when they are opened. A blister located near module 30 would probably have traces corresponding to a plurality of more distant blisters running closely adjacent to it. In opening that blister a careless, distracted or mentally dulled patient might well damage adjacent traces, falsely signaling that other blisters had also been opened when in fact they remained intact. This possibility gravely impacts the reliability of any such digital system.
FIG. 3 represents a typical prior art analog electronically monitored card, while FIG. 4 shows the corresponding circuit as a schematic diagram. Except as described below, all parts are the same as in the digital version shown in FIGS. 1 and 2.
The analog version differs in that a separate conductive trace need not run from each spatially extended trace pattern to a separate input on electronics module 30. Instead, a plurality of such trace patterns 32a, 32b, 32c, and so forth are connected in series, sharing a common connection a single module 30 input such as 42a through traces 20a and 20b or the like.
Just as in the digital version, trace patterns 32a, 32b and so forth are placed behind the blisters formed in sheet 10 so as to be broken when corresponding blisters are opened. A card may hold either just one series network of such trace patterns, connecting those corresponding to all blisters on the card, or a plurality of such networks, each for instance connecting the traces corresponding to blisters in just one row or column.
Obviously, with no further elaboration, such a network could detect only the first trace breakage in the series. An additional “bridging” trace such as 50a, 50b or 50c, having a significantly higher resistance per unit length than other traces on the card, is therefore placed in parallel with each yet in such a location as to remain safe from damage when blisters are opened. As a result, when each pattern-forming trace is broken, its corresponding resistive trace remains, forming an electric “bridge” across the gap. The network's total resistance will thus increase by steps as successive blisters are opened, each step equal to the resistance of one bridge.
Bridging traces 50a, 50b, 50c, and the like, are typically made from a different conductive material from that in the other traces on the card, and having an inherently much higher resistance per unit length. For example, in a screen-printing process where the low-resistance traces are formed by silver-bearing ink, the resistive traces might be formed by an ink bearing carbon instead.
Such traces, and the materials used to form them, will hereafter be referred to as “conductive” and “resistive” respectively, regardless of the fact that they differ only in the relative amounts of resistance present. The word “ink” will be used in a general sense to mean any trace-forming material, whether applied through screen printing or by any other process, with the understanding that screen printing is a conceptually simple process generally representative of all others.
The total resistance RT of such a series network can be read by any of several methods well-known in the art of electrical measurement. For example, a known source voltage Vs can be applied between an output 44 and an input such as 42a on module 30. By Ohm's Law, the measured current Im flowing in the network will equal the source voltage divided by the network resistance, and if all bridges have equal resistance Rb, Im will equal Vs/n Rb where n is the number of blisters opened. Alternatively, a known source current Is can be sent through the network and the resulting voltage Vm, equal to nIsRb, can be measured. This latter method is used in virtually all modern digital ohmmeters. Measurement functions are performed by circuitry, typically including an analog-to-digital converter (ADC) plus an auxiliary current-sensing resistor or fixed-current source, wholly housed within module 30.
This method of blister opening detection avoids the major disadvantages of the digital one since, as can be seen from FIG. 2, it dramatically reduces the numbers of required traces and needed microcontroller inputs: from one per blister plus one or more supply traces, down to one for a whole group of blisters—typically one or even a plurality of rows or columns—plus, again, one or more supply traces. This can bring cost savings both in microcontroller capacity and in conductive trace material. The drastic reduction in trace number also permits the remaining traces to be wider and hence more rugged, making accidental breakage less likely.
The analog method, unfortunately, brings problems of its own, caused by the difficulty in making traces with resistance values both closely reproducible and high enough to be useful.
Again taking screen printing as an example, resistive inks depend on contact (or at least near-contact, permitting electron tunneling) between adjacent carbon particles embedded in a binder material. Heavily-loaded inks have much inter-particle contact and thus low resistivities, but those resistivities are closely reproducible: much as the number of cars comprising a railroad train passing a given point is closely reproducible, since all are evenly spaced. A more lightly-loaded ink has less contact and thus higher resistivity, but that resistivity is less reproducible due to variable spacing between particles within the binder material: much as the number of automobiles passing a given point on a highway may vary widely due to the wider, and more widely variable, distances between them than between railroad cars.
For the bridges in an analog network to have consistent values, therefore, an ink with low intrinsic resistivity (high carbon loading) must be chosen. Such an ink is usually given a sheet resistance rating in “ohms per square” by the manufacturer, meaning that if the shape of a trace having the nominal applied thickness is approximated by a series of squares, its total resistance after processing will be roughly the number of squares multiplied by the sheet resistance. Typical sheet resistance values lie in the range from 10 to 100 Ω/square at a nominal 0.025-millimeter (1-mil) thickness.
Consider, for example, the four resistive traces shown in Table 1 and representative of those which might be used in a blister-package application. Trace 1 here serves as a benchmark, with Traces 2, 3 and 4 each varying from it in only one of the three variables of trace length, trace width and ink resistance, as indicated in each case by an asterisk. For comparison, Trace 5 varies in both length and width but in such a way as to have the same number of squares and thus the same total resistance as Trace 1. All variables for each trace are assumed to be constant at the nominal values shown.
TABLE 1Ink sheetTotal traceLength,Width,resistance,resistance,TracemillimetersmillimetersSquaresΩ/sqohms11000.52005010,0002 200*0.54005020,00031001.0*10050 500041001.0200 10* 20005 200*1.0*2005010,000
As is readily seen, increasing the trace's length or the ink's sheet resistance will increase the resistance, as will decreasing the width of the trace. In general, the trace resistance Rt is closely approximated by the equation Rt=LRs/W, where L is the trace's length, W its width, and Rs the sheet resistance of the ink after processing. Minor corrections must be made if the trace makes bends or angles. For example, the square at the corner of a sharp 90-degree bend contributes only about one-half of the usual resistance since most of the current passing through it travels a path shorter than its full width. Such corrections are well-known in the art of thick-film, thin-film and semiconductor resistor design.
Any damage to the trace, even if it does not completely interrupt it, will change its resistance, since, in the vicinity of the break, comparatively many, much smaller squares are needed to approximate its shape. Printed resistive traces must therefore be guarded from damage.
To permit accurate measurement without requiring impractically high currents in a microcontroller-based system, resistors must have values in the range of at least several hundred ohms and thus require “square counts” typically in the range of a few dozen squares and upward. To fit such a trace on a printed (screen-printed or otherwise) blister pack requires that it be either physically large, or folded up compactly. Neither of these options may allow it to be fitted into regions of the blister pack where it is safe from damage by someone carelessly or distractedly opening a blister. The alternative is to place each resistive bridge in a location far from the blister it represents, resulting in a proliferation of low-resistance connecting traces and thus bringing back the disadvantages of the digital system.
Even given a suitable geometry and an ink with a consistent sheet resistance, a number of processing variables can affect the final resistance values. In screen printing, for example, these variables are likely to include the initial quality of the stencil, how many times it has been used, the temperature (affecting the viscosity of the ink and thus how freely it passes through the stencil), the sharpness of the rubber squeegee (affecting the pressure of the ink at the point where it is forced through), the humidity (affecting the printed surface and how well the ink wets it or spreads across it once it has passed through the stencil), and the orientation of the trace with respect to the direction in which the squeegee passes across the stencil. Stencils are also likely to vary slightly one from another, even given identical line art or Gerber files, due to differences in image development or in the stencil materials themselves.
As a result, while for a given original design all resistive traces on any given finished card are likely to have similar ratios, their actual values are likely to differ slightly between any one card and another, and more severely between cards made on successive days, on different production runs, with different stencils, and so forth. Any resistance-based analog method for blister opening detection must therefore take these differences into account.
An examination of the prior art suggests that most, if not all, such methods heretofore suggested fail to address this issue well enough for consistently reliable operation.